The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin, China.
TEDA Institute of Biological Sciences and Biotechnology, Tianjin Key Laboratory of Microbial Functional Genomics, Nankai University, Tianjin, China.
Nat Commun. 2021 Feb 9;12(1):879. doi: 10.1038/s41467-021-21186-4.
Salmonella Typhimurium establishes systemic infection by replicating in host macrophages. Here we show that macrophages infected with S. Typhimurium exhibit upregulated glycolysis and decreased serine synthesis, leading to accumulation of glycolytic intermediates. The effects on serine synthesis are mediated by bacterial protein SopE2, a type III secretion system (T3SS) effector encoded in pathogenicity island SPI-1. The changes in host metabolism promote intracellular replication of S. Typhimurium via two mechanisms: decreased glucose levels lead to upregulated bacterial uptake of 2- and 3-phosphoglycerate and phosphoenolpyruvate (carbon sources), while increased pyruvate and lactate levels induce upregulation of another pathogenicity island, SPI-2, known to encode virulence factors. Pharmacological or genetic inhibition of host glycolysis, activation of host serine synthesis, or deletion of either the bacterial transport or signal sensor systems for those host glycolytic intermediates impairs S. Typhimurium replication or virulence.
鼠伤寒沙门氏菌通过在宿主巨噬细胞中复制来建立全身感染。在这里，我们表明感染鼠伤寒沙门氏菌的巨噬细胞表现出糖酵解上调和丝氨酸合成减少，导致糖酵解中间产物的积累。丝氨酸合成的影响是由细菌蛋白 SopE2 介导的，SopE2 是编码在致病性岛 SPI-1 中的 III 型分泌系统 (T3SS) 效应物。宿主代谢的变化通过两种机制促进鼠伤寒沙门氏菌的细胞内复制：葡萄糖水平降低导致细菌摄取 2-和 3-磷酸甘油酸和磷酸烯醇丙酮酸（碳源）的上调，而丙酮酸和乳酸水平的增加诱导另一个致病性岛 SPI-2 的上调，该岛编码已知的毒力因子。抑制宿主糖酵解、激活宿主丝氨酸合成，或缺失细菌对这些宿主糖酵解中间产物的运输或信号传感器系统，都会损害鼠伤寒沙门氏菌的复制或毒力。
